Production of NVB302, a type B lantibiotic, has begun at DSM’s site in Italy.
DSM BioSolutions entered into an agreement with Novacta Biosystems for the process development and cGMP production of its C. difficile molecule, NVB302. The product will initially be used for preclinical and Phase I trials.
DSM reports that process development has been completed and cGMP manufacturing has started at its microbial fermentation facility in Capua, Italy. “We have chosen to work with DSM as it has an impressive track record for scaling up fermentation processes for antibacterial agents from actinomycetes,” notes Mike Dawson, CSO of Novacta.
Novacta Biosystems, a U.K. biotechnology company controlled by Celtic Pharma, is focused on bringing anti-infectives with improved resistance profiles to the market. Besides NVB302, NVB333 has been selected for preclinical development for Gram-positive nosocomial infections, and the Gram-negative nosocomial infection program is at the lead optimization stage.
Novacta’s product development is based on a class of compounds produced by bacteria called lantibiotics (lanthionine-containing antibiotics). Lantibiotics are highly post-translationally modified peptides containing a rare, dimeric amino acid called lanthionine, the firm explains. Due to the presence of these dimeric amino acids, the compounds have multiple ring structures.
The type A lantibiotics have a rod-shaped structure and many have antibacterial activity mediated by formation of pores in the bacterial membrane. Novacta’s programs are based on type B lantibiotics, which have a higher degree of cyclization and are not pore forming.
The company has developed methods for structural manipulation of lantibiotics to improve therapeutic and pharmaceutical properties. Novacta cloned and sequenced the biosynthetic pathways to key members of the class B lantibiotics. Systems have been established that allow rapid, parallel modifications of the amino acid sequences and screening of the progeny lantibiotics, the firm notes.
Novacta is also developing a technique for in vitro biosynthetic modification, which will further extend the range of chemistries that can be achieved. The company says that it has also developed and applied synthetic methodologies for derivation of both the natural and variant molecules.
The company’s antibacterial lantibiotics act as inhibitors of cell wall biosynthesis by binding the biosynthetic intermediate lipid II. This is considered a good target from a resistance perspective as it is not the product of a single gene and cannot readily mutate to a resistant form.
Glycopeptides, another class of antibacterials, also work in this way. Novacta says that its compounds, however, bind at a different binding site to the glycopeptides and there is no cross-resistance.
